Khurshid Andrabi - Academia.edu (original) (raw)

Papers by Khurshid Andrabi

Members of Shc (src homology and collagen homology) family, p46shc, p52shc, p66shc have known to ... more Members of Shc (src homology and collagen homology) family, p46shc, p52shc, p66shc have known to be related to cell proliferation and carcinogenesis. Whereas p46shc and p52shc drive the reaction forward, the role of p66shc in cancers remains to be understood clearly. Hence, their expression in cancers needs to be evaluated carefully so that Shc analysis may provide prognostic information in the development of carcinogenesis. In the present study, the expression of p66shc and its associate targets namely Eps8 (epidermal pathway substrate 8), Rac1 (ras-related C3 botulinum toxin substrate1) and Grb2 (growth factor receptor bound protein 2) were examined in fresh tissue specimens from patients with esophageal squamous cell carcinoma and esophageal adenocarcinoma using western blot analysis. A thorough analysis of both esophageal squamous cell carcinoma and adenocarcinoma showed p66shc expression to be significantly higher in both types of carcinomas as compared to the controls. The con...

Temporal Temperature gradient gel electrophoresis (TTGE)2 in combination with PCR and ‘GC-clampin... more Temporal Temperature gradient gel electrophoresis (TTGE)2 in combination with PCR and ‘GC-clamping’ has proven highly efficient as a method for detection of DNA sequence differences. Duplex DNA fragments differing by single base substitutions can be separated by electrophoresis in Temporal Temperature gradient gels. To increase the number of single-base changes that can be distingished by TTGE, we used the polymerase chain reaction to attach a 50-base-pair G+C-rich sequence, designated a GC-clamp, to one end of amplified DNA fragments that encompass regions of the human bFGF promoter region. The melting properties and electrophoretic behavior of a 215 base pair DNA fragment containing a bFGF promoter are changed by 1 Corresponding author: andrabik@kashmiruniversity.net 2 Abbreviations: bFGF: basic Fibroblast Growth Factor; PCR: Polymerase Chain Reaction; TTGE: Temporal Temperature Gradient Gel Glectrophoresis Aeijaz-Ul-Noor, Sabia Rashid, Khurshid I. AndrabiSingle base variation in ...

Pathology & Oncology Research, 2018

Rearranged during transfection (RET) is a proto oncogene implicated in thyroid carcinogenesis of ... more Rearranged during transfection (RET) is a proto oncogene implicated in thyroid carcinogenesis of papillary type (PTC). The RET proto-oncogene in PTC is constitutively activated by fusion of its tyrosine kinase domain with the 5´region of another gene thereby generating chimeric products collectively named RET/PTCs. RET/PTC1 and RET/PTC3 are best characterized among all RET/PTC rearrangements. Kashmir valley has witnessed an alarming increase in thyroid cancer incidence in young women. Therefore, we investigated the occurrence of RET/PTC 1 & 3 rearrangements by semi quantitative and qPCR in thyroid cancer patients (n = 48) of Kashmiri population and interrelated results with various clinicopathological characteristics. We observed that all the RET/PTC rearrangements were confined to PTC cases (10/40). Presence of RET/PTC rearrangement significantly correlated with gender, elevated TSH levels and lymph node metastasis. Overall, our study advocates that RET/PTC3 rearrangement is a frequent event in the carcinogenesis of thyroid gland in Kashmiri population although a study with a larger sample size is needed to get a clear scenario.

Journal of Cellular Physiology

Copyright © 2014 Mehvish Showkat et al. This is an open access article distributed under the Crea... more Copyright © 2014 Mehvish Showkat et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. mTOR is a central nutrient sensor that signals a cell to grow and proliferate.Through distinct protein complexes it regulates different levels of available cellular energy substrates required for cell growth. One of the important functions of the complex is to maintain available amino acid pool by regulating protein translation. Dysregulation of mTOR pathway leads to aberrant protein translation which manifests into various pathological states. Our review focuses on the role mTOR signaling plays in protein translation and its physiological role. It also throws some light on available data that show translation dysregulation as a cause of pathological complexities like cancer and the available drugs that target the pathway for cancer...

(BVr) ribosomal protein S6 kinase (S6K1) is mediated by an event other than phosphorylation

Frontiers in Clinical Drug Research - Anti-Cancer Agents, 2021

Cortinarius is the largest genus of mushroom forming fungi with several subgenera having ectomyco... more Cortinarius is the largest genus of mushroom forming fungi with several subgenera having ectomycorrhizal associations with coniferous trees and other plants. In view of limited studies on this speciose genus from the Himalayan region, a morpho-molecular phylogenetic approach was employed to study this taxon. Phylogenetic analysis and Bayesian inference of nuc rDNA internal transcribed spacer region ITS1-5.8S-ITS2 (ITS barcode) separated these sequences along with the identical sequences from Gene bank into three distinct clads with high bootstrap values suggesting the possibility of new taxa. The new species were found to possess some diagnostic features that separated them from other closely related species in each section. Based on our study in the Kashmir Himalayan forests, we report three new species of Cortinarius from the Indian subcontinent. The identified species, C. cibum, C. neocephalixus, and C. nigricans belong to subgenera Myxacium, Phlegmacium and Telamonia. A taxonomi...

International journal of biochemistry and molecular biology, 2021

High Myopia (HM) is a common complex-trait eye disorder. There is essential evidence that genetic... more High Myopia (HM) is a common complex-trait eye disorder. There is essential evidence that genetic factors play a significant role in the development of nonsyndromic high myopia. Identification of susceptibility genes of high myopia will shed light on the pathophysiological mechanism underlying their genesis. This was a case control study examining the prospect of association of DLGAP1, EMILIN2 & MYOM1 genes on MYP2 locus in purely ethnic (Kashmiri) population representing a homogeneous cohort. Genomic DNA was extracted using phenol chloroform and salting out method. Extracted DNA was genotyped for polymorphic variations in MYOM1, EMILIN2 and DLGAP1 genes involving Sanger di-deoxy method. Allele frequencies were tested for Hardy-Weinberg disequilibrium in 224 cases and compared with 220 emmetropic controls. In DLGAP1, documented single nucleotide polymorphism (SNP); Pro517Pro was observed. A previously reported Asn451Asn SNP was observed in EMILIN2. MYOM1 showed five polymorphic vari...

Homeostasis - An Integrated Vision, 2019

S6 kinase, a member of AGC family of protein kinases and a downstream effector of mTORC1 pathway ... more S6 kinase, a member of AGC family of protein kinases and a downstream effector of mTORC1 pathway has over the years found much relevance in maintaining a normal cellular state by virtue of its established role in regulation of cell growth and proliferation. S6 kinase activity has been linked to different cellular processes like glucose homeostasis, translational and transcriptional regulation. Hence any dysregulation in S6K1 leads to the emergence of various pathological conditions like diabetes, cancer and obesity. It is as such S6 kinase has emerged as a potential target for therapeutic interventions employed in curing such diseases. The Present Chapter reviews the regulation of S6K1, its structural organization and functions, besides highlighting its potential to act as an alternative therapeutic target for various cancerous situations exhibiting deranged mTOR signaling so as to overcome the possibility of relapses observed otherwise while using conventional drugs

Knowledges on Thyroid Cancer [Working Title], 2019

Thyroid cancers are malignant tumors in the thyroid gland. DNA polymorphisms are playing a decisi... more Thyroid cancers are malignant tumors in the thyroid gland. DNA polymorphisms are playing a decisive role in unscrambling the genomic basis of tumor formation and development in cancer. Thyroid cancer is influenced in a polygenic and low-penetrance manner by RET gene polymorphisms and this part of the world (North India) has not recorded any study regarding RET alterations in this very cancer. We assessed RET G691S (rs1799939), L769L (rs1800861) and S904S (rs1800863) polymorphisms by restriction fragment length polymorphism (RFLP) in order to explain their potential role in the diagnosis and prognosis of Papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). In RET G691S polymorphism, the total dissemination of variant alleles (GA + AA) was 62.9% in cases as related to 44.5% in controls (P < 0.05). RET L769L variant alleles (TG + GG) was 70% in cases versus 88% in controls (P < 0.05). In RET S904S, occurrence of variant alleles (CG + GG) was 56% in cases versus 44% in controls (P < 0.05). G691S and L769L polymorphism advocate a "Dominant mode of inheritance". The S904S polymorphism approves an "Additive mode of inheritance". In conclusion, there was an over-representation of RET G691S/S904S polymorphisms and underrepresentation of L769L polymorphism in PTC and FTC patients. Additionally, our data suggest that some haplotypes (A T G, G T G and A T C) of RET may act as low penetrance alleles for predisposition of thyroid cancer.

Meta Gene, 2017

a-Lactalbumin (a-La) gene is involved in milk production traits in dairy animals. The variability... more a-Lactalbumin (a-La) gene is involved in milk production traits in dairy animals. The variability in milk production potentials of different animals have been attributed to the polymorphism existing within this gene. The study was carried out to detect polymorphism in PCR amplified DNA fragments encompassing to-363 to +80 of the a-La gene in 50 Holstein Friesians (HF), 63 Jersey and 49 endogenous Kashmiri cattle. The polymorphism was detected by sequence analysis of amplified products. Three genotypes designated as AA, AB, BB were observed during the course of the study. The two alleles were differentiated on the basis of three single nucleotide polymorphism (SNP) each at position-250,-89, and-46 of the promoter region of the a-La gene. All the three nucleotide variations involved base transition viz, A to G, T to C and A to G, respectively. The haplotype with nucleotide A, T and A at positions-250,-89 and-46 was designated as A whereas the haplotype with nucleotide G, C and G at positions-250,-89 and-46 was designated as Allele B. The genotypic frequencies were observed to be 90.50 % (n=57) for AA allele and 9.50% (n=06) for AB allele in Jersey, however no animal with genotype of BB allele was observed. The genotypic frequencies of homozygous A, homozygous B and heterozygous AB were 30% (n=15), 22% (n=11) and 47% (n=23), respectively in Kashmiri cattle. Like in Jersey breed of cattle, no homozygous animal was observed to harbor BB genotype in HF cattle and the frequencies of AA and AB genotypes were 70% (n=35) and 30% (n=15), respectively. The allele frequencies for A and B allele were 95.25% and 4.75% in Jersey, 85% and 15% in HF and 54% and 46% in Kashmiri cattle, respectively. In view of the breed averages and preponderance of A allele in Bos tarus, it can be largely inferred that the polymorphism in 5' flanking region of the a-La gene could be a potential molecular marker for production traits in dairy cattle. However, to authenticate it further evaluation through association studies are warranted.

International Journal of Diabetes in Developing Countries, 2015

Activation of MC4R gene has been shown to inhibit appetite and increase basal metabolic rate whil... more Activation of MC4R gene has been shown to inhibit appetite and increase basal metabolic rate while deficiency leads to obesity, hyperphagia, severe hyperinsulinemia, increased linear growth and decrease in metabolic activity, facts that drew strong attention as a possible cause of obesity and diabetes. In this study, we aimed to investigate the sequence variations of MC4R gene in a diabetic population of the Kashmir region and work out association of such variations (if any) with the disease phenotype. No such study has ever been taken up in the Jammu and Kashmir State, despite the existence of a significant population of type 2 diabetic patients. A total of 420 samples (200 with type 2 diabetes and 220 controls) were taken. Genomic DNA was extracted from whole blood samples using standard protocols like salting out and proteinase k. The specific fragments of DNA were amplified and hence then purified. Purified amplicons were subjected to heteroduplex assay to screen for SNPs/mutations. Samples which showed heteroduplex bands were sent for sequencing. The genotype and allele frequencies were evaluated using the χ2 tests or the Fisher exact tests. We here report one novel heterozygous mutation, i.e. C to T at codon 7 in diabetic patients. The results showed significant differences in the 7C/T genotype (p < 0.001) and allele (p < 0.0001) frequencies between type 2 diabetes mellitus and control subjects. The fasting blood sugar (FBS), postprandial blood sugar (PPBS) and random blood sugar (RBS) levels were higher with CT genotype in type 2 diabetes mellitus patients but difference was not found statistically significant. C to T substituting arginine with cysteine appeared to associate with type 2 diabetes in the Kashmiri population. Insilico predictions show that substitutions likely have an impact on structure and functional properties of protein making it imperative to understand their functional consequences in relation with diabetes and obesity.

P16INK4A a tumour suppressor protein is found frequently mutated in a variety of human cancers. W... more P16INK4A a tumour suppressor protein is found frequently mutated in a variety of human cancers. We have previously identified a novel 7 base pair deletion that associates with esophageal squamous cell carcinoma (ESCC). Here we describe its functional consequences through 3 D modeling, insilico structural analysis and ligand docking. Our data indicates that the structural perturbations, together with energy changes impose a serious constraint on the mutant protein to optimally interact with its ligands (CDK4 and CDK6).

Cancer is not just one disease, but a generic term used to encompass a group of more than two hun... more Cancer is not just one disease, but a generic term used to encompass a group of more than two hundred diseases sharing common characteristics. From a clinical point of view, cancer is a large group of diseases, that vary in their age of onset, rate of growth, state of cellular differ‐ entiation, diagnostic detectability, invasiveness, metastatic potential, response to treatment, and prognosis. From a molecular and cell biological point of view, however, cancer may be a relatively small number of diseases caused by similar molecular defects in cell function resulting from common types of alterations to a cell’s genes. Ultimately, cancer is a disease of abnormal gene expression. There are a number of mechanisms by which this altered gene expression occurs. These mechanisms may occur via a direct insult to DNA, such as a gene mutation, translocation, amplification, deletion, loss of heterozygosity, or via a mechanism resulting from abnormal gene transcription or translation. The overal...

Cell Cycle

ABSTRACT Eukaryotic translation initiation factor 4E was recently shown to be a substrate of mTOR... more ABSTRACT Eukaryotic translation initiation factor 4E was recently shown to be a substrate of mTORC1, suggesting it may be a mediator of mTORC1 signaling. Here, we present evidence that eIF4E phosphorylated at S209 interacts with TOS motif of S6 Kinase1 (S6K1). We also show that this interaction is sufficient to overcome rapamycin sensitivity and mTORC1 dependence of S6K1. Furthermore, we show that eIF4E-TOS interaction relieves S6K1 from auto-inhibition due to carboxy terminal domain (CTD) and primes it for hydrophobic motif (HM) phosphorylation and activation in mTORC1 independent manner. We conclude that the role of mTORC1 is restricted to engaging eIF4E with S6K1-TOS motif to influence its state of HM phosphorylation and inducing its activation.

The Indian Journal of Animal Sciences, 2013

Lactalbumin is a major whey protein, readily available from natural sources. It was isolated and ... more Lactalbumin is a major whey protein, readily available from natural sources. It was isolated and purified to homogeneity from bovine milk. The purified α-lactalbumin was chemically modified using acetic anhydride to acetylate the amino groups of surface lysine residues. Acetylation resulted in conformational change in the protein which was reflected by change in its hydrodynamic properties such as stokes radius and relative elution volume. The modified variants were characterized to indicate the increase in their stokes radius and decrease in the relative elution volume due to conformational change in the protein.

Colorectal Cancer - Surgery, Diagnostics and Treatment, 2014

Sex Men are more likely than women to develop colorectal cancer. The incidence rate of colorectal... more Sex Men are more likely than women to develop colorectal cancer. The incidence rate of colorectal cancer between 2000 and 2004 was 69.2 per 100,000 population among men and 45.8per 100,000 populations among women [10]